The invention relates to an innovative use of gelatin and a cross-linking agent for producing a cross-linking therapeutic composition, which forms a cross-linked gelatin gel as a cell matrix in a target area of the human or animal body.
In particular, the invention relates to the use of such a therapeutic composition for treating damage to intervertebral discs, cartilage, menisci, tendons or bone in humans or animals.
Biocompatible, biodegradable matrix materials are used in different fields of medicine. Therapeutic applications, in which the biodegradable material serves as cell matrix, i.e. as a matrix supporting the growth, proliferation and/or differentiation of cells, play an important role therein. These include applications, in which the matrix material is applied or administered cell-free and possibly in conjunction with growth factors in order to perform a growth- or regeneration-promoting function in the target area of the body, as well as applications, in which the matrix material is already colonised by cells in vitro. In the case of the last-mentioned applications, a precultivation of the cells in or on the matrix material can be conducted in vitro, wherein a so-called tissue implant is formed that is then used at the location of the body to be treated. Examples of the described methods are the treatment of bone defects using biomaterials and growth factors (e.g. thrombocyte growth factors or BMPs (bone morphogenetic proteins)) or the treatment of cartilage defects using autologous or allogenic cartilage cell transplantation.
The matrix materials most frequently used for the specified purposes are biopolymers based on proteins or polysaccharides, in particular collagen, gelatin, hyaluronic acid, chitosan or alginates. Preferred forms of application of these materials are gels or sponge structures, which because of their structure allow the cells to be distributed as uniformly as possible. In the case of soluble polymers such as gelatin, for example, these must generally be used in cross-linked form to be able to produce matrices that are dimensionally stable under physiological conditions and have a sufficiently long life. Such shaped bodies based on cross-linked gelatin are described, for example, in the German Patent Application DE 10 2004 024 635 A1.
A further indication, in which a treatment with tissue-specific cells is applicable, is damage to or degeneration of the intervertebral disc, in particular the nucleus pulposus (gelatinous core). A degeneration of the tissue of the nucleus pulposus that can occur with increased likelihood with advancing age leads to higher stress on the annulus fibrosus (fibrous ring), which can ultimately result in it being damaged and thus lead to a prolapsed intervertebral disc.
The intervertebral disc cells of the nucleus pulposus do not have a sufficient capability to regenerate themselves. Therefore, the process of biological intervertebral disc reconstruction is used to prevent the above-described consequences. In this case, intervertebral disc cells or mesenchymal stem cells are cultivated in vitro and then administered to the nucleus pulposus of the patient. A further possibility is to administer suitable growth and differentiation factors to the intervertebral disc using a biomaterial that develop a locally restricted efficacy there and thus contribute to the regeneration of the intervertebral disc. However, it is not possible to implant a solid matrix combined with growth factors or colonised by cells into the nucleus pulposus, since this would inevitably be associated with significant damage to the annulus fibrosus.
For this reason, the cells, the growth factors or a combination of both in a liquid medium, e.g. in a nutrient solution or the like, are injected into the intervertebral disc. However, there is a problem in that the injection path cannot be adequately closed and therefore the cells and/or growth factors suspended in the liquid medium can be pressed out of the intervertebral disc again through the injection path as soon as pressure is exerted on it.